Asthma is the most common chronic disease of childhood, and asthma prevalence and incidence have been increasing over the past several decades. This population-based cohort study of risk factors for asthma in school-aged children offers an opportunity to address this important, poorly understood chronic childhood disease. The results from the CHS provide leads for reducing the burden of asthma. In high ozone communities, physician diagnosis of asthma in the CHS was associated with time spent outside and with playing team sports, factors which increase exposure and ventilation rates. Obesity was associated with new onset asthma; pets accounted for a substantial proportion of the attributable risk; and interaction was observed between a prototype air pollutant, cigarette smoke, and GSTP1, an enzyme involved in the metabolism of oxidants present in air pollution. To expand on these findings, the investigators propose to establish a new cohort of 6,000 kindergarten, first, and second grade children, enriched with children who play team soccer. The diagnosis of incident asthma cases in each of the 12 communities will be confirmed by a standardized clinical examination. Information on physical activity will be obtained from team sport participation and pedometry. The extensive air pollution monitoring system in each of the 12 communities will be enhanced by measurement of N02, 03, PM2.5 and CO at homes, schools and areas where children exercise. Individual exposures will be assigned using spatial mapping techniques and micro-environmental models. A case-control study of new asthmatics will provide an opportunity to: (1) replicate associations between asthma and genes involved in the response to reactive oxygen species; (2) clarify the temporal association between asthma onset and exposure to pets and other indoor allergens; and (3) evaluate interactions between air pollution and indoor allergens, and between exposure to ambient air pollution and polymorphisms in genes involved in the response to reactive oxygen species. This proposal presents innovative approaches to defining the asthma phenotype in large epidemiologic studies, physical activity assessment, exposure assessment, and genetic epidemiology.